14.12. 2017, Biologie tukové tkáně

PhD project: Effects of antidiabetic lipids on major metabolic pathways

White adipose tissue (WAT) is a complex endocrine organ and its low-grade inflammation in obesity contributes to the development of metabolic disorders. In 2014, a class of WAT-born lipid mediators - fatty acid esters of hydroxy fatty acids (FAHFA) was discovered. FAHFAs are endogenous lipids with anti-inflammatory and anti-diabetic properties, including the enhancement of glucose tolerance, and insulin and glucagon-like peptide 1 (GLP-1) secretion while reducing inflammatory responses. They consist of a fatty acid (e.g. palmitic acid, PA) esterified to the hydroxyl group of a hydroxy fatty acid (e.g. hydroxystearic acid, HSA), abbreviated as PAHSA. The position of the branching carbon defines a regioisomer (e.g. 5-PAHSA). There are several regioisomer families derived from palmitic, palmitoleic, stearic, oleic, linoleic, and docosahexaenoic acid with tissue-specific distribution documented so far. Adipose tissue represents a major site of FAHFAs synthesis, but the biosynthetic enzymes involved are unknown. Serine hydrolase carboxyl ester lipase and threonine hydrolases were identified as FAHFA-metabolizing enzymes. In humans, FAHFAs were detected in the serum, breast milk, meconium, and adipose tissues. The aim of the project is to explore the metabolism of FAHFA using metabolomics, lipidomics and proteomics. The work is based on cell cultures, animal models as well as human samples and large dataset processing is an integral part of the project.

Candidate’s profile (requirements):

Highly motivated students with completed Master degree (or those expecting to obtain their degree this year) with a background in biochemistry, physiology, cell biology, biostatistics, medicine or related fields should apply.  We expect dedication, scientific creativity and the ability and interest to work in an interdisciplinary team. Experience with in vivo (mouse) and/or in vitro cell models is a plus.

Relevant publications:

Brezinova M, et al. Biochim Biophys Acta. 2018;1863(2):126-31. http://dx.doi.org/10.1016/j.bbalip.2017.11.004

Kuda O, et al. Diabetes. 2016;65(9):2580-90. http://dx.doi.org/10.2337/db16-0385

Kuda O, et al. Diabetes 2018;67(6):1190-1199. https://doi.org/10.2337/db17-1087

Kuda O, Cell Metabolism 2018;28(4):541-542. https://doi.org/10.1016/j.cmet.2018.09.006

Supervisor: RNDr. Ondrej Kuda, Ph.D.